AUTHOR=Tafet Gustavo E. , Ortiz Alonso Tomas TITLE=Learned helplessness and learned controllability: from neurobiology to cognitive, emotional and behavioral neurosciences JOURNAL=Frontiers in Psychiatry VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1600165 DOI=10.3389/fpsyt.2025.1600165 ISSN=1664-0640 ABSTRACT=The sustained and prolonged exposure to environmental stressors may provoke different reactions, depending on the subjective perception of control. Repeated perception of lack of control may lead to learned helplessness, which has been linked to the development of depression. It has been shown that learned helplessness is associated with increased activation of the serotonergic dorsal raphe nucleus (DRN) and the amygdala, as well as the decreased activation in certain regions of the prefrontal cortex (PFC), such as the dorsolateral (DL-PFC) and the ventromedial prefrontal cortex (VM-PFC). Perception of control has been associated with increased activation of the DL-PFC and the VM-PFC, decreased activation of the DRN and the amygdala, as well as increased activation of the serotonergic medial raphe nucleus (MRN). It is also associated with decreased activation of the ventral hippocampus and increased activation of the ventral striatum, including the nucleus accumbens (NAc). Functionally, perception of control promotes the implementation of active coping strategies, characterized by efficient cognitive-emotional processing, effective decision making, and goal directed actions, that in turn may lead to lower anxiety, greater tolerance of adverse events, emotional stability, and increased resilience. Just as it has been demonstrated that helplessness may result from a learning process, it could be hypothesized that controllability may also be trained and learned. If so, learned controllability could be taught to enhance resilience and provide invaluable resources ultimately reducing depressive symptoms and improving overall well-being. By fostering a sense of controllability, where individuals learn to associate their actions with desired outcomes, it may be possible to counteract the consequences of “learned helplessness” aspects of depression. This could provide direction in development of novel interventions aimed at promoting skill acquisition, problem-solving strategies, and adaptive decision-making, thereby restoring a sense of agency and resilience in the face of adversity.